Retroviral vectors have been used to express foreign genes in target cells for research, gene therapy, etc. Retroviral vectors can be produced with a relatively simple method, and also have some advantages, such as, to introduce foreign genes into the chromosomes of the host. Normally, viral proteins localized in the viral envelope play a crucial role in retroviral vector infection. Much effort has been expended to widen the range of host cells to which the vectors can infect or to develop viral vectors which infect only specific cells by modifying the envelope proteins of retroviral vector.
For example, a system, where VSV-G protein is integrated into the retroviral vector envelope, has been developed to ensure the infectivity to a broader range of host cells (H. Yu et al., 1999, Gene Therapy, 6, 1876-1883). VSV-G is a protein expressed on the surface of envelope of vesicular stomatitis virus, which is infectious to a considerably broad range of host cells. In addition, for example, Sendai virus F protein has been used as an envelope protein by way of experiment. An F protein-pseudotyped retrovirus was found to exhibit specific infectivity to asialoglycoprotein receptor-positive cells (M. Spiegel et al., 1998, Hepatology, 28, 1429-1429; M. Spiegel et al., 1998, J. Virology, 72, 5296-5302).
However, these conventional pseudotype retroviruses have only insufficient infectivity to various tissues and cells. For example, a variety of stem cells including hematopoietic stem cell can be important target cells in gene therapy or the like (Y. Hanazono, Molecular Medicine, Vol. 36, No. 7, 1999), but most stem cells are in nondividing state (Abkowitz, J. L. et al., Nat Med, 2 (2), 190-7, 1996). In general, it is difficult to introduce genes using the retroviral vector exhibiting low infectivity against such nondividing cells. Further, the vector system using conventional techniques has failed to introduce genes into extracellular matrix-abundant cells such as lung airway mucosal epithelial cells. A method for introducing genes into these types of cells requires physically removing extracellular matrix, such as mucus, by welshing. However, this method is complicated and tissues can be damaged.